Lupus autoantibodies in Cancer therapy

· TGI - Biomarkers, TGI - Cancer

Systemic lupus erythematosus (SLE) is distinct among autoimmune diseases because of its association with circulating autoantibodies reactive against host DNA.

The precise role that anti-DNA antibodies play in SLE pathophysiology remains to be elucidated, and potential applications of lupus autoantibodies in cancer therapy have not previously been explored.

In the current study the unexpected finding that a cell-penetrating lupus autoantibody, 3E10, has potential as a targeted therapy for DNA repair–deficient malignancies are reported.

It was found that

– 3E10 preferentially binds DNA single-strand tails,

– inhibits key steps in DNA single-strand and double-strand break repair, and

– sensitizes cultured tumor cells and human tumor xenografts to DNA-damaging therapy, including doxorubicin and radiation.

The results establish an approach to cancer therapy that is applicable to BRCA2-related malignancies such as breast, ovarian, and prostate cancers and also raise the possibility that lupus autoantibodies may be partly responsible for the intrinsic deficiencies in DNA repair and the unexpectedly low rates of breast, ovarian, and prostate cancers observed in SLE patients.

In an another study published by J. M. Ford, in Sci. Transl. Med. 4, 157fs38 (2012) shows that A lupus causing anti-DNA antibody penetrates living cells and targets DNA repair for therapeutic advantage in human cancer cells.

These observations suggest

– the potential use of a lupus anti-DNA antibody in cancer therapy and

– identifies lupus autoantibodies as a potentially rich source of therapeutic agents.




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